RESUMEN
The cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells. In this study, we assessed the ability of SVN to bind to the envelope GP of Zaire Ebola virus (ZEBOV) and inhibit its replication. SVN interacted specifically with the protein's mucin-rich domain. In cell culture, it inhibited ZEBOV replication with a 50% virus-inhibitory concentration (EC50) of 50 nM, and was also active against the Angola strain of the related Marburg virus (MARV), with a similar EC50. Injected subcutaneously in mice, SVN reached a peak plasma level of 100 nm in 45 min, but was cleared within 4h. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6h, beginning the day before virus challenge, 9 of 10 animals survived the infection, while all infected, untreated mice died. When treatment was begun one hour or one day after challenge, 70-90% of mice survived. Quantitation of infectious virus and viral RNA in samples of serum, liver and spleen collected on days 2 and 5 postinfection showed a trend toward lower titers in treated than control mice, with a significant decrease in liver titers on day 2. Our findings provide further evidence of the potential of natural lectins as therapeutic agents for viral infections.
Asunto(s)
Antivirales/uso terapéutico , Proteínas Bacterianas/uso terapéutico , Proteínas Portadoras/uso terapéutico , Ebolavirus/efectos de los fármacos , Lectinas/uso terapéutico , Proteínas del Envoltorio Viral/metabolismo , Replicación Viral/efectos de los fármacos , Animales , Antivirales/administración & dosificación , Antivirales/metabolismo , Antivirales/farmacología , Proteínas Bacterianas/administración & dosificación , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/farmacología , Proteínas Portadoras/administración & dosificación , Proteínas Portadoras/metabolismo , Proteínas Portadoras/farmacología , Modelos Animales de Enfermedad , Ebolavirus/fisiología , Glicoproteínas/metabolismo , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/virología , Concentración 50 Inhibidora , Inyecciones Subcutáneas , Lectinas/administración & dosificación , Lectinas/metabolismo , Lectinas/farmacología , Hígado/virología , Marburgvirus/efectos de los fármacos , Proteínas de la Membrana , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Suero/virología , Bazo/virología , Análisis de Supervivencia , Carga ViralRESUMEN
A presença de sinais e sintomas de alteração vestibular são freqüentes nos idosos e o impacto dos déficits vestibulares podem ser incapacitantes, principalmente naqueles que são privados de estimulação neurossensorial por institucionalização. Avaliaram-se sinais e sintomas de alteração vestibular com questões subjetivas e equilíbrio estático e dinâmico com testes específicos. A descrição da sintomatologia vestibular foi relatada pelos idosos, dando subjetividade à avaliação. No entanto, nos testes físicos de equilíbrio, há indicativos importantes de alteração vestibular. O estudo apontou que, por estarem inseridos em ambiente com estimulação neurossensorial inadequada, idosos institucionalizados apresentam maior prevalência de alterações vestibulares.
